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加蓬的1型O组艾滋病毒感染:流行率低,但1型O组艾滋病毒基因多样且耐药毒株在传播。

HIV type-1 group O infection in Gabon: low prevalence rate but circulation of genetically diverse and drug-resistant HIV type-1 group O strains.

作者信息

Liégeois Florian, Boué Vanina, Butel Christelle, Mouinga-Ondémé Augustin, Sica Jeanne, Zamba Chantal, Peeters Martine, Delaporte Eric, Rouet François

机构信息

Laboratoire de Rétrovirologie, CIRMF (Centre International de Recherches Médicales de Franceville), Franceville, Gabon.

出版信息

AIDS Res Hum Retroviruses. 2013 Jul;29(7):1085-90. doi: 10.1089/aid.2012.0375. Epub 2013 Mar 8.

Abstract

The goals of this study conducted in Gabon were to determine the prevalence rate of HIV-1 group O (HIV-1/O) infections and to characterize the genetic diversity of HIV-1/O strains as well as implications on antiretroviral (ARV) drug resistance. During 2010-2011, 1,176 samples from HIV-positive subjects were tested at the CIRMF (Centre International de Recherches Médicales de Franceville) retrovirology laboratory using an in-house serotyping assay. Plasma HIV-1/O RNA viral loads (VL) were determined using the Abbott RealTime HIV-1 assay. After full genome sequencing, drug resistance patterns were analyzed using two different algorithms (Agence Nationale de Recherches sur le SIDA et les hépatites virales and Stanford). Overall, four subjects (0.34%) were diagnosed as HIV-1/O infected. One subject, untreated by ARVs, died 2 months after HIV-1/O diagnosis. One was lost to follow-up. Two additional patients, treated with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, showed CD4 counts <200/mm(3) and VL results of 101,000 and 10,050 cp/ml. After full-length genome sequencing of these two strains, we found a wide range of natural polymorphism in the protease (≥15 substitutions) and gp41 (N42D mutation) genes, as well as in the gag and gag-pol cleavage sites. No resistance mutation was detected in the integrase gene. These two strains harbored the Y181C mutation making them resistant to NNRTIs. M41L, M184V, and T215Y mutations were also found for one strain, making it resistant to all NRTIs by the Stanford algorithm. Even if HIV-1/O infection is low in Gabon, an accurate diagnosis and a reliable virological follow-up are required in Central Africa to optimize ARV treatments of HIV-1/O-infected patients.

摘要

在加蓬开展的这项研究的目的是确定HIV-1 O组(HIV-1/O)感染的流行率,描述HIV-1/O毒株的基因多样性及其对抗逆转录病毒(ARV)药物耐药性的影响。在2010年至2011年期间,在中法维尔国际医学研究中心(CIRMF)逆转录病毒实验室使用内部血清分型检测法对1176份来自HIV阳性受试者的样本进行了检测。使用雅培实时HIV-1检测法测定血浆HIV-1/O RNA病毒载量(VL)。在进行全基因组测序后,使用两种不同算法(法国国家艾滋病和病毒性肝炎研究机构以及斯坦福算法)分析耐药模式。总体而言,4名受试者(0.34%)被诊断为HIV-1/O感染。1名未接受抗逆转录病毒治疗的受试者在HIV-1/O诊断后2个月死亡。1名失访。另外两名接受基于非核苷类逆转录酶抑制剂(NNRTI)方案治疗的患者,CD4细胞计数<200/mm³,病毒载量结果分别为101,000和10,050 cp/ml。对这两株病毒进行全长基因组测序后,我们在蛋白酶(≥15个替换位点)和gp41(N42D突变)基因以及gag和gag-pol裂解位点发现了广泛的自然多态性。在整合酶基因中未检测到耐药突变。这两株病毒携带Y181C突变,使其对NNRTIs耐药。其中一株病毒还发现了M41L、M184V和T215Y突变,根据斯坦福算法使其对所有核苷类逆转录酶抑制剂耐药。即使加蓬的HIV-1/O感染率较低,但在中非仍需要准确诊断和可靠的病毒学随访,以优化对HIV-1/O感染患者的抗逆转录病毒治疗。

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